tbuckley/cabot-search huggingface dataset:
Abstract 10199: Increased Aortic Wall Shear Stress in Marfan Patients Long-Term After Proximal Grafting Assessed by 4D Flow Cardiac Magnetic Resonance
Authors: Alice Saffioti, maria chiara palumbo, Katherine Tak, Emiliano Votta, Jay D Humphrey, Yadong Wang, Nicole Liberman, Parmanand SINGH, Jiwon Kim, Richard B Devereux, Mary J Roman, Mario F Gaudino, Leonard N Girardi, alberto redaelli, Jonathan W Weinsaft
Journal: Circulation (2022)

Introduction: For Marfan syndrome patients (MFS) with thoracic aortic aneurysms (TAA), prosthetic graft surgery provides lifesaving benefits, but adverse event risk persists in the native aorta for which mechanism is unclear. Sustained impact of proximal grafts on biomechanics within and distal to grafts is unknown. Methods: MFS patients with chronic (&gt; 6 month) proximal grafts were compared to non-surgical MFS (nsMFS) and age/sex matched controls: Wall shear stress (WSS) on 4D flow cardiac MRI and size (diameter) were quantified at aortic landmarks (ascending, arch, descending, thoracoabdominal). Results: 34 subjects were studied including MFS late (7.3±6.7 years) after graft implantation (n=12). Post-surgical MFS were of similar age (p=0.93) and sex (p=0.64) to controls but older than non-surgical MFS (45±10 vs 33±11 yo, p=0.01): In the ascending aorta (grafted territory), post-surgical MFS had higher WSS (1.17±0.55 Pa) than nsMFS (0.74±0.17 Pa) and controls (0.60±0.17 Pa; p=0.002 for trend). Similarly, in the (native) descending aorta, WSS was higher in post-surgical (1.06±0.24 Pa) than nsMFS (0.97±0.11) and controls (0.83±0.16; p=0.02) ( Figure ) paralleling results in the arch (p=0.06) and a similar trend in the thoracoabdominal aorta (p=0.12). Among the overall MFS cohort (n=23), proximal graft implantation associated with increased WSS in the ascending and descending aorta (both p&lt;0.01) in analyses controlling for age and aortic size in respective territories ( Table ). Conclusions: Prosthetic grafts yield sustained alterations in aortic biomechanics, including elevated WSS (a marker of adverse remodeling) in grafted regions and the distal native aorta.
Abstract 10335: Implementation of a Population Health Infrastructure for Hypertension in a Primary Care Clinic Setting
Authors: Jevin Yabut, Erica Becker, Ina Lico, Erind Muco, Cunegundo Vergara
Journal: Circulation (2022)

Introduction: In 2021, 48% of patients in the Hartford Hospital Adult Primary Care (APC) Clinic with a diagnosis of hypertension had controlled blood pressures of &lt;140/90 compared to 63% in Hartford Healthcare (HHC) as a whole. This demonstrates potential healthcare disparities within the APC clinic, whose patient panel consists primarily of an underserved Hispanic population with Medicare, Medicaid or are uninsured and lack overall health literacy. The aim of this project is to have 75% of APC patients with hypertension to have blood pressures of &lt;140/90 by 2023. Methods: The team implemented standardized staff and resident training regarding blood pressure measurement and ACC/AHA Hypertension Guidelines with pre- and post- training surveys. Residents reviewed their patient roster to schedule appointments for those with uncontrolled hypertension. The team created an Epic SmartPhrase to incorporate standard work by all providers for initial and follow-up hypertension visits. This included blood pressure-lowering medications, environmental risk factors, evaluation for obstructive sleep apnea, and recommendations for nonpharmacological interventions. Staff implemented standardized workflow which included: repeat blood pressure measurement after 5 minutes of rest for blood pressures &gt;140/90, ensuring proper documentation of repeat blood pressure in correct field in Epic, and scheduling 3-week follow-up appointments for blood pressure management. The clinic has been approved for a grant for BP monitors for those without health insurance. Results: In May 2022, 52% (727/1409) of patients at APC had blood pressures of &lt;140/90 compared to 38% (104453/272615) at HHC. Conclusion: Implementation of standardized staff and resident training, Epic SmartPhrases, and clinic workflow may lead to improved blood pressure control in an academic primary care clinic. Future direction includes assessing if optimizing BP control leads to improved patient outcomes.
Abstract 10096: Genetic Control of Lysosomal Dysfunction Reprograms Sterol Metabolism in Pulmonary Arterial Hypertension
Authors: Lloyd D Harvey, Hee-Jung J Kim, Mona Alotaibi, Yi-Yin Tai, Ying Tang, Sanya Arshad, Wei Sun, Haodi Wu, Jingsi Zhao, Anna Kirillova, Chen-shan J Woodcock, Adam Handen, Yassmin Al Aaraj, Miranda K Culley, Neha Hafeez, Annie Watson, Callen Wallace, Haodi Wu, Mara G Sullivan, Claudette M St. Croix, Donna Stolz, Gang Li, Chase Corley, Jeffrey G McDonald, Mehdi Nouraie, Tae-Hwi Schwantes-An, Ankit A Desai, Michael Pauciulo, Bill Nichols, Robert Lafyatis, Raymond L Benza, Thomas Bertero, Mohit Jain, Stephen Y Chan
Journal: Circulation (2022)

Background : Vascular inflammation critically regulates endothelial pathophenotypes, yet causative mechanisms remain incompletely defined, particularly in pulmonary arterial hypertension (PAH). Immune dysregulation and metabolic reprogramming are recognized tenets of PAH pathogenesis, but a unifying theory connecting the two has not been established. Methods &amp; Results: Guided by an unbiased, metabolome-wide association study from the multicenter PAH Biobank cohort (N=2,666) that identified a proinflammatory sterol and bile acid metabolite plasma signature significantly associated with PAH mortality (adjusted P values&lt;1.1x10 -6 ), we found in pulmonary arterial endothelial cells (ECs) that induction of the nuclear receptor coactivator 7 (NCOA7) tempered the generation of proinflammatory sterols by bolstering lysosomal acidification and constraining EC immunoactivation. Conversely, reduced NCOA7 promoted lysosomal dysfunction, resulting in sterol- and bile acid-driven inflammation and EC phenotypes consistent with PAH. Notably, the common variant intronic SNP rs11154337 in NCOA7 was found to control NCOA7 levels, lysosome activity, sterol and bile acid production, and EC immunoactivation in isogenic, CRISPR-Cas9, SNP-edited, iPSC-derived ECs, indicating a potentially widespread genetic predisposition to NCOA7 deficiency. Correspondingly, SNP rs11154337 was associated with PAH severity as noted by six-minute walk distance ( P =0.0130, β=58.15, 95% CI [14.45-119.36]) and mortality ( P =0.0250; hazard ratio=0.4368, 95% CI [0.21-0.90]) in an independent, single-center PAH cohort (N=93). In vivo , mice deficient for Ncoa7 or treated with exogenous 7α-hydroxy-3-oxo-4-cholestenoic acid (7HOCA)—chosen as a representative metabolite from the sterol signature associated with mortality in the PAH Biobank—demonstrated worsened hemodynamic and histological indices of PAH. Conclusions: Our work establishes a genetic and metabolic paradigm that links lysosomal biology and sterol and bile acid processes with EC inflammation. This paradigm carries broad implications not only on molecular diagnostic and therapeutic development in PAH but also in other vascular disorders dependent upon acquired and innate immune regulation.
Abstract 10484: Carotid Plaque Score Adds Discriminatory Benefit to the Stress Echo for Major Adverse Cardiovascular Events in Low-Intermediate Risk Cardiac Patients
Authors: Murray Matangi, Marie-France Hetu, David Armstrong, Shellenberger Jonas, Daniel Brouillard, Josh Bakker, Ana Johnson, Amer M Johri
Journal: Circulation (2022)

Introduction: Carotid plaque is recommended for cardiac risk stratification for intermediate risk patients but has not been integrated into cardiology community clinics to help refine testing and reduce risk for major adverse cardiovascular events (MACE). The purpose was to determine the clinical usefulness of carotid plaque score (PS) to guide management of low-intermediate risk patients. Methods: Patients 40-75 years who received a carotid ultrasound were followed up to 10 years for MACE (cardiovascular death, myocardial infarction, stroke). Low-intermediate risk participants (n = 9,114) with no known cardiovascular disease were included. Administrative data holdings housed at IC/ES were used for event follow-up. Kaplan-Meier curves and Cox proportional hazard ratios determined relative risk. Combining plaque score (Rotterdam method, plaque presence within carotid segments, PS 0 to 6) with stress echo (SE) was assessed in a subset of participants (n = 624). Results: The optimum threshold for PS = 2 for 1-year MACE (AUC = 0.738). The population rate of MACE over 10 years was 4%. In participants referred for SE, PS of &lt;2 was associated with an excellent 5-year outcome irrespective of the SE result (PS&lt;2 = 0.9% MACE, normal SE = 1.6% MACE). A PS of ≥2 and an abnormal SE was associated with increased risk (MACE = 11%). The hazard ratio for MACE increased with PS from 1.08 to 9.86 (PS = 1 and 6; reference PS=0). Combining SE with PS (either test positive) increased the sensitivity of the SE from 36% to 71%, with an excellent specificity (SE alone = 94% vs SE+PS = 87%). Conclusions: In low-intermediate risk patients, if a PS is &lt;2, cardiac testing for atherosclerotic risk is not required for up to 5 years. However, patients with a PS of ≥2 should undergo a stress echo. Combining SE with PS adds discriminatory benefit in identifying risk for MACE. This simple stratification parameter can be easily integrated in community cardiology clinics to prioritize patients requiring further testing.
Abstract 10001: Relationship Between Coronary HIPs on Non-Contrast T1-WI by CMR and Vulnerable Plaque Features by NIRS-IVUS
Authors: Tatsuya Fukase, Dohi Tomotaka, Shinichiro Fujimoto, Yui Nozaki, ryota nishio, Ayako Kudo, Mitsuhiro Takeuchi, Norihito Takahashi, Yuichi Chikata, Endo Hirohisa, Yuko Kawaguchi, Shinichiro Doi, Hiroki Nishiyama, Makoto Hiki, Iwao Okai, Hiroshi Iwata, Takayuki Yokoyama, Shinya Okazaki, Katsumi MIYAUCHI, Hiroyuki Daida, Tohru Minamino
Journal: Circulation (2022)

Introduction: Although high-intensity plaques (HIPs) on cardiac magnetic resonance (CMR) have been reported to be associated with vulnerable plaque features, there is little evidence in comparison with near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) findings, which have recently been shown to positively identify vulnerable plaques and predict peri-procedural myocardial infarction (pMI). Hypothesis: We assumed that the coronary plaque characterization of CMR and NIRS-IVUS may have a significant relationship, and determined whether pre-percutaneous coronary intervention (PCI) evaluation using CMR identifies HIPs at risk of pMI. Methods: In total, 52 patients with stable coronary artery disease who underwent CMR with non-contrast T1-weighted imaging and PCI using NIRS-IVUS were studied. HIP was defined as a signal intensity of the coronary plaque-to-myocardial signal intensity ratio (PMR) ≥1.4. We evaluated the association between the NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI 4mm ) and plaque morphology on IVUS, and assessed the incidence of pMI. Results: Of 62 lesions, HIPs were observed in 30 lesions (48%). HIPs had a significantly higher maxLCBI 4mm (500±170 versus [vs.] 288±218, p &lt;0.001) and plaque burden (69±8% vs. 63±10%, p =0.011) than the non-HIPs. The correlation between the maxLCBI 4mm and PMR was significantly positive (r=0.51). In multivariable analysis, HIP independently predicted a maxLCBI 4mm ≥400 (odds ratio [OR]=3.93; 95% confidence intervals [CIs]: 1.21-13.6, p =0.023). Furthermore, pMI occurred in 14 of 30 lesions (47%) with HIP, compared to 5 of 32 lesions (16%) without HIP ( p =0.005). Conclusions: We found an important relationship between coronary HIPs on CMR and NIRS-derived maxLCBI 4mm . We also confirmed that non-contrast T1-weighted imaging in CMR can be useful not only for the characterization of vulnerable plaque features, but also for pre-PCI risk stratification.
Abstract 10351: Racial Differences in Chronic Stress or Allostatic Load Variation Due to Androgen Deprivation Therapy in Prostate Cancer
Authors: Nickolas Stabellini, Jennifer Cullen, Justin Moore, Lifen Cao, Neeraj Agarwal, Biplab Datta, Jorge Garcia, John Shanahan, Kristin Waite, Nelson Hamerschlak, Alberto Montero, Jill Barnholtz-Sloan, Avirup Guha
Journal: Circulation (2022)

Introduction: The cumulative burden of chronic stress and life events can be measured by Allostatic load (AL), whose high values are related to poorer health outcomes and increased risk of cardiovascular disease (CVD). The primary objective of this study is to analyze the impact of androgen deprivation therapy (ADT) on AL variation in patients upon diagnosis of prostate cancer (PC). Hypothesis: ADT may increase AL variation in prostate cancer patients. Methods: Data were obtained from a Cleveland area integrated health care systems informatics platform. The initial cohort included males ≥18 years diagnosed with PC between 2005 and 2022. AL was calculated using multiple markers representing the cardiovascular, metabolic, and immune systems ( Table 1 ) before diagnosis and monthly during the first year. ADT use was captured based on prescribed medications. A linear-mixed-effects model, adjusted for patient demographics, CVD risk factors, and cancer characteristics, and treatment, was used to study AL monthly variation. The analysis was stratified by Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) race. Results: We analyzed a total of 7,168 PC adenocarcinoma patients (31.7% NHB vs 68.3% NHW), of which 20.9% received ADT. NHBs had higher AL pre-PC diagnosis than NHWs (p=0.001). AL monthly variation was 0.15 (±0.02) higher in all PC patients on ADT (p&lt;0.001) and these results persisted stratifying by race (0.10 ± 0.04 for NHBs, p=0.01 and 0.16 ± 0.03 for NHW, p&lt;0.001). There was no racial difference between AL increase in those receiving only ADT (0.09 +/- 0.04; p = 0.06). The details of individual AL variable measures pre-PC diagnosis and the mixed-effects model are presented in Table 1. Conclusion: Pre-PC-diagnosis chronic stress/AL is higher among NHBs vs. NHWs with the addition of ADT increasing AL in both races after PC diagnosis. This study is hypothesis-generating, offering data that help explain, in part, the racial differences in ADT-mediated CVD.
Abstract 10913: Causes of Early Mortality After Catheter Ablation of Atrial Fibrillation
Authors: Min Choon Tan, Pattara Rattanawong, Abhishek Deshmukh, Komandoor Srivathsan, Luis Scott, Christopher J McLeod, Samuel J Asirvatham, Peter A Noseworthy, Yong-Mei Cha, Siva K Mulpuru, Justin Z Lee
Journal: Circulation (2022)

Background: Recognition of the causes of early mortality after atrial fibrillation (AF) catheter ablation is essential for the improvement of patient safety. Objective: This study sought to determine the causes of early mortality (≤90-days) after AF ablation and to further understand the circumstances surrounding death after the procedure. Methods: We performed a retrospective analysis of AF ablation from January 1, 2013, to December 1, 2021 at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Causes of death were identified through a comprehensive chart review of the electronic health record from within the Mayo Clinic system and outside records when available. Results: A total of 6,723 patients were included in the study. The 30-day and 90-day all-cause mortality rates were 0.09% and 0.22%, respectively. Among all 90-day deaths, majority of the deaths (73.3%) did not have a direct relationship with the procedure. Sudden death was the most common cause of early death (20%), followed by peri-procedural stroke (13%), respiratory failure (13%), atrioesophageal fistula (13%), infection (7%), heart failure (7%), and traumatic brain injury (7%). The 90-day mortality rate directly due to AF ablation procedural complications was 0.06%. Most of the early deaths (93.3%) occurred after discharge from index hospitalization, among which 64.3% were readmitted before their death, 14% died at home, and 7% were discharged on comfort care and died in hospice. The main reason for readmission leading to death was respiratory failure (33%). Conclusion: Atrial fibrillation ablation procedure has a 90-day mortality of 0.22% and the most common cause of early mortality was sudden death. The majority (73.3%) of early mortality was not directly associated with a procedural complication, and the mortality rate due to complications associated with the AF ablation procedure was 0.06%.
Abstract 10706: Transnitrosation From the NO-Receptor Soluble Guanylyl Cyclase to Oxidized Thioredoxin-1 Has a Potential Cardiovascular Protective Effect Against Oxidative Stress
Authors: WAQAS YOUNIS, Chuanlong Cui, Ping shu, Yong Qin, Annie V Beuve
Journal: Circulation (2022)

Soluble guanylyl cyclase (GC1) is an α/β heterodimer producing cGMP when stimulated by nitric oxide (NO). The NO-GC1-cGMP pathway is essential for cardiovascular homeostasis. Oxidative stress is known to disrupt the NO-GC1-cGMP pathway via oxidation of GC1 cysteines, which makes it unresponsive to NO stimulation. Under these conditions, GC1-α subunit “moonlights” by increasing cellular S-nitrosation via specific transfer of its nitrosothiols to cysteines of other proteins (transnitrosation). One of the SNO-targets identified by Mass Spectrometry (MS) was the oxidized form of Thioredoxin1 (oTrx1), which is unidirectionally transnitrosated by GC1 with αC610 as a SNO-donor and C73 of Trx1 as the SNO-recipient. Because oTrx1 itself drives transnitrosation, we sought and MS-identified SNO-proteins targeted by both GC1 and Trx1, suggesting a SNO-GC1→oTrx1→targets cascade. We investigated the (patho)physiological relevance of GC1-dependent transnitrosation activity by creating a knock-in (KI) mice with replacement of αC610 to a serine (αC610S). Biotin switch assays confirm that, under oxidative stress (Angiotensin II (AngII) treatment), global and Trx1 levels of S-nitrosation (SNO) were drastically reduced in lungs and hearts of KI mice compared to WT but the NO-stimulated GC1 activity was similar between WT and KI. Importantly, telemetry recordings indicated that 2 weeks of AngII treatment led to a more severe increase in BP and a more prolonged QTc in KI mice. The AngII-induced rise in MBP was 27.6 ± 2.5 mmHg in KI vs 21.6 ± 1.2mmHg in WT, while AngII-increase in QTc, reflecting delayed repolarization, was 12.53 ± 2.30ms in KI vs. 8.713 ± 2.72ms for the WT. The elevated BP with AngII treatment correlated with higher increase in cardiac hypertrophy, oxidation (measured by DHE staining) and fibrosis (picric acid staining) in KI mice. The AngII-induced increase in a) hypertrophy in KI was 0.63 ± 0.07 vs. 0.24 ± 0.08 mg/g in WT, b) cardiac oxidation was 0.19 ± 0.07 in KI and negligible in WT, and c) fibrosis was 1.75 (A.U) in KI vs. 1.31 in WT. These more severe cardiovascular dysfunctions in KI mice in response to AngII suggest that transnitrosation by GC1, potentially using oTrx1 as a nitrosothiol relay, is a mechanism of protection against oxidative stress.
Abstract 10433: Inhibition of Plasminogen Activator Inhibitor Type 1 in Experimental Venous Thrombosis
Authors: Maxim E Shaydakov, Joshua Rainey, Daniel A Lawrence, Fedor Lurie, Jose A Diaz
Journal: Circulation (2022)

Introduction: Conventional treatment of deep vein thrombosis is suboptimal, requiring continuous improvement in knowledge about the disease and a search for new therapeutic approaches. Hypothesis: Blood flow affects the composition of an acute venous thrombus (VT). Aim 1: Compare VT composition under flow and stasis conditions. Aim 2: Evaluate the antithrombotic properties of the novel PAI-1 inhibitor MDI-2268 in-vivo. Methods: C57BL/6 mice, 10-12w, 20-25g were used in electrolytic (EIM) and ligation (LM) models of venous thrombosis. Aim 1: The thrombus weight (TW) and the microstructure of an acute VT (Day 2) in the EIM (n=5) and the LM (n=5) were compared. Expression of PAI-1, tPA, and uPA in the vein wall and plasma levels of D-dimer were investigated. Aim 2: Five EIM groups (n=5) were studied: MDI-2268 1.5 mg/kg (Group 1), MDI-2268 3 mg/kg (Group 2), enoxaparin 7.3 mg/kg (Group 3), MDI-2268 3 mg/kg plus enoxaparin 1.8 mg/kg (Group 4), and DMSO controls (Group 5). TW and bleeding time (BT) on Day 2 were measured. Results: Aim 1: VT within the EIM was smaller compared to the LM (6.2.5±3.6 vs. 26.2±3.6, P&lt;0.05). VT formed within the EIM had a significantly higher amount of plasminogen. The level of D-dimer was 23.4±12.5 and 4.5±1.3 ng/mL/mg in the EIM and LM, respectively (p&lt;0.05). Aim 2: TW was 6.9±3.3 (p&gt;.05), 5.5±1.6 (p=.035), 3.8±1.3 (p=.005), and 4.8±2.4 mg (p=.035) for groups 1,2,3, and 4; compared to 12.7±5.7 mg in the controls. BT was not affected by the MDI-2268. Conclusions: Blood flow pattern significantly affects VT composition. Non-occlusive thrombus has a higher potential to be targeted by the fibrinolytic system due to a higher plasminogen content. MDI-2268 demonstrates strong antithrombotic properties in-vivo and may be associated with a lower risk of bleeding compared to enoxaparin. This data may contribute to a better understanding of the disease process, different outcomes after venous thrombosis, and new therapeutic targets.
Abstract 11015: Pacemaker Lead Insertion Sites Contribute to Regional and Global Ventricular Dysfunction
Authors: Daniel A Castellanos, Ashwin Prakash, Stephen Sanders, Chrystalle Katte Carreon, Matthias Sigler, Edward Oleary, Chris Baird, Francis Fynn-Thompson, Kimberlee Gauvreau, Sunil J Ghelani, Douglas Mah
Journal: Circulation (2022)

Introduction: Ventricular pacing can cause dysfunction but how the lead is anchored to the myocardium has not been studied. We evaluated patterns of regional and global ventricular function in patients with a ventricular pacemaker or defibrillator using cine cardiac CT (CCT). Methods: This was a single center retrospective study of patients with a ventricular pacemaker or defibrillator who underwent a cine CCT from September 2020 to June 2021. Regional wall motion abnormalities (RWMAs) were assessed in relation to lead insertion site (sew-on vs screw-in) and pacing activity (active vs. inactive). Results: A total of 122 ventricular lead insertion sites were analyzed in 43 patients (53% male, median age 20 years, range 3-57 years). Thirteen patients (30%) had palliated single ventricle physiology, twenty-nine patients had congenital heart disease with biventricular circulation (67%), and one patient had a structurally normal heart (2%). RWMAs were present in 51/122 (42%) lead insertion sites among 23/43 (53%) patients. The prevalence of a lead insertion site associated RWMA was higher with active pacing (54% vs 19%; p &lt; 0.001) and highest for active epicardial sew-on sites ( Figure 1 ). RWMAs were not associated with position of the insertion site relative to the chest wall (p = 0.85) or the distance between the two heads of a bipolar lead (p = 0.23). Patients with lead insertion site associated RWMAs had a lower systemic ventricular ejection fraction (mean of 37.5% vs 52.5%, p &lt; 0.001) compared to those without a RWMA. Conclusions: Pacemaker lead insertion site RWMAs are common and associated with systemic ventricular dysfunction. The mechanism and clinical significance of this regional and global dysfunction warrant further study.